Risk of revision arthroplasty surgery after exposure to physically demanding occupational or leisure activities: A systematic review

Introduction Lower limb arthroplasty is successful at relieving symptoms associated with joint failure. However, physically-demanding activities can cause primary osteoarthritis and accordingly such exposure post-operatively might increase the risk of prosthetic failure. Therefore, we systematically reviewed the literature to investigate whether there was any evidence of increased risk of revision arthroplasty after exposure to intensive, physically-demanding activities at work or during leisure-time. Methods We searched Medline, Embase and Scopus databases (1985—July 2021) for original studies including primary lower limb arthroplasty recipients that gathered information on physically-demanding occupational and/or leisure activities and rates of revision arthroplasty. Methodological assessment was performed independently by two assessors using SIGN, AQUILA and STROBE. The protocol was registered in PROSPERO [CRD42017067728]. Results Thirteen eligible studies were identified: 9 (4,432 participants) after hip arthroplasty and 4 (7,137participants) after knee arthroplasty. Narrative synthesis was performed due to considerable heterogeneity in quantifying exposures. We found limited evidence that post-operative activities (work or leisure) did not increase the risk of knee revision and could even be protective. We found insufficient high-quality evidence to indicate that exposure to physically-demanding occupations increased the risk of hip revision although “heavy work”, agricultural work and, in women, health services work, may be implicated. We found conflicting evidence about risk of revision hip arthroplasty associated with either leisure-time or total physical activities (occupational or leisure-time). Conclusion There is currently a limited evidence base to address this important question. There is weak evidence that the risk of revision hip arthroplasty may be increased by exposure to physically-demanding occupational activities but insufficient evidence about the impact on knee revision and about exposure to leisure-time activities after both procedures. More evidence is urgently needed to advise lower limb arthroplasty recipients, particularly people expecting to return to jobs in some sectors (e.g., construction, agriculture, military).


Introduction
Hip and knee replacements have been routinely indicated for the treatment of end-stage arthritis over the past 40 years [1,2]. The demand for these operations is increasing both because of the ageing population but also because of growth in rates of surgery amongst people aged < 60 years. According to data from the National Joint Registry, the number of primary hip and knee replacements performed in England, Northern Ireland and Wales amongst people aged below 60 years increased by 25% and 20% respectively from 2010 to 2018 [3]. Future projections point towards an even greater increase by 2030 and 2035 [4][5][6].
Although highly effective interventions [7,8], hip and knee replacements may fail over time necessitating revision surgery to the replaced joint. Revision surgery is more complex than primary arthroplasty with poorer outcomes [9] and a greater economic burden on health services [10,11]. Survival rates after arthroplasty are lower amongst younger recipients. One studied reported higher failure rate in hip arthroplasty recipients aged <60 years [12]. Another study reported that, compared with the 15% lifetime risk of revision amongst those aged 60 years, rates of hip revision were 29.6% and of knee revision were 35.0% amongst those aged 50-54 years [13]. These age differences are at least partly explained by sex (greater risk among male recipients) but also by different indications for primary surgery, type of prosthesis and fixation method [14] but there is need for a better understanding of the impact of other factors on implant survival.
Modern arthroplasty techniques derive from the 1960s (hip) and 1970s (knee). Since then, there have been vast improvements in component materials, geometry and fixation as well as surgical techniques, leading to shorter length of hospital stay, more conservative surgery and better outcomes. Concerned about the consequences of damage to the prostheses, surgeons in the past generally urged caution to patients about their participation in sport and LTPA. Moreover, lower limb arthroplasty surgery was typically offered relatively late in the course of joint failure and thus the majority of patients were elderly and not expecting to return to the labour market. Despite the limited evidence against engaging in LTPA post arthroplasty, the consensus amongst orthopaedic surgeons has been to advise caution [15].
There is considerable evidence that exposure to physically-demanding work which mechanically loads the hip (e.g. heavy lifting) or knee (e.g. kneeling), increases the risk of primary osteoarthritis at those sites [16][17][18][19]. People aged <60 years at the time of their arthroplasty are likely to need to return to their occupation and possibly engage in other physicallydemanding activities during leisure-time. A previous systematic review evaluated the evidence that host factors were associated with aseptic loosening after arthroplasty [20]. They identified three studies involving 178 hip arthroplasties which reported "activity levels" and an increased risk of aseptic loosening after total hip arthroplasty (THA). Unfortunately, this review did not separate activities occurring at work from those occurring outside the workplace. Furthermore, although aseptic loosening is a common mechanism necessitating revision surgery, it only accounts for 25% of hip revision arthroplasties [21] and 20% of knee revision operations [22]. Therefore, to fill this gap, we undertook a systematic review of the published literature in order to explore the evidence about the risk of revision arthroplasty surgery related to physically-demanding activities performed (a) at work and (b) during leisure-time.

Material and methods
A protocol of the systematic review was registered in PROSPERO (registration number CRD42017067728). Following the Population, Intervention, Comparison and Outcome (PICO) format, our research question was as follows: amongst adults aged over 18 years at the time of primary hip or knee arthroplasty, undertaken for any common indication, what was the effect of exposure to physically-demanding activities (a) at work and (b) in leisure on the risk of revision surgery performed for any reason other than for reasons of infection.

Search strategy
Our search was conducted in three electronic databases: MEDLINE and Embase using the Ovid search engine, and in Scopus (S1 File), limited to studies published in peer-reviewed journals, from January 1985 to week 5 June 2021 (in Medline), and 7 July 2021 (in Embase and Scopus), in English or Spanish languages. Duplicates were removed, and letters, notes, editorials and editorial commentaries were also excluded. However, when a conference abstract was found, we checked whether a full paper was subsequently published. In addition, reference lists from all full papers retrieved, as well as the systematic reviews found during the search, were checked to find any additional relevant studies not covered by the MeSH terms or key words used in the search.

Inclusion and exclusion criteria
To be eligible for inclusion, publications were randomised controlled trials, case-control or cohort studies including adults with primary hip or knee arthroplasty, followed-up for more than 12 months post-operatively, and in whom information was collected about either, or both, physically-demanding occupational or leisure-time activities and in which rates of revision arthroplasty were recorded. We excluded those studies that investigated: i) patients with only inflammatory arthritis or other specific rarer pathologies (e.g., haemophilia); ii) hip or knee surgical procedures other than total replacement and joints other than hip or knee; iii) risk factors related to operative procedure or nature of prosthesis only (e.g., surgical approach); and iv) non-elective arthroplasties. Studies were also excluded if: participants were under 18 years of age at the time of the arthroplasty; the indication for revision arthroplasty was exclusively infection; or the outcome measured was not revision surgery (e.g. volume of polyethylene wear).

Screening
Screening of titles and abstracts was initially undertaken by one reviewer (EZ) who classified papers as "eligible", "ineligible" or "uncertain whether eligible or not" for inclusion in the review. A second reviewer (ECH and CHL), checked all papers classified as uncertain to be suitable for inclusion (n = 229) and where consensus was not reached, discussed with a third reviewer (KWB). Additionally, a random sample of 10% of those deemed by the first reviewer as "eligible" or "ineligible" were also screened by a second reviewer but it was demonstrated that none of these papers had been misclassified. Once full text papers had been agreed and selected, two reviewers (EZ, ECH or CHL) independently reviewed the full texts for suitability for inclusion. Discrepancies were discussed by both reviewers and, if consensus was not reached, with a third reviewer (KWB).

Data extraction
Data were extracted from included articles independently by two reviewers (EZ and ECH / CHL) according to a pre-defined proforma. Data extraction included: author and year of publication, study design, country, site of procedure, duration of follow-up, indication for primary arthroplasty, sample size, age at the time of primary operation and age at revision (if provided), number lost to follow-up, operation-related factors, definition of revision, type of physical activity (undertaken at work and/or during leisure time), method of measurement of physical activity including how exposure to physical activity that loads the joint was categorised (e.g. "active vs inactive" or "high, medium, low"), covariates considered, risk estimates and source of funding where available. Findings from the data extracted were reported according to exposure to physical activity: i) occupation and occupational activities, ii) leisure-time physical activities (LTPA), and iii) total physical activity.

Quality assessment
To evaluate the methodological quality to address our specific research question (S1 and S2 Tables), we used a modified version of the Scottish Intercollegiate Guidelines Network (SIGN) checklist for observational studies [23] alongside the Assessment of Quality in Lower Limb Arthroplasty (AQUILA) checklist (which was specifically developed to assess quality of lower limb arthroplasty studies) [24] for cohort studies and the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) [25] checklist for case-control studies. Two reviewers (KWB, EZ) independently assessed each study, and subsequently compared their ratings, discussing any discrepancies until consensus was reached about any potential bias and the direction of its effect.

Results
In total, 20,274 citations were identified. Only three further citations, published prior to 1985, were retrieved by hand searching bibliographies of relevant papers and systematic reviews. After removing duplicates, 11,307 titles and abstracts were screened, yielding 50 studies that were potentially relevant, for which full texts were obtained (Fig 1). Assessment of the full text publications resulted in the exclusion of a further 37 studies, leaving 13 papers eligible for inclusion in this review. Table 1 summarises the main characteristics of the 13 studies retrieved. Published between January 1983 and July 2021, nine related to risk of revision after primary THA [26][27][28][29][30][31][32][33][34], and four the risk of revision after primary total knee arthroplasty (TKA) [35][36][37][38]. In terms of study design, there were ten longitudinal studies; two prospective [29,30] and eight retrospective studies [26, 27, 31-33, 35, 37, 38], and three case-control studies [28,34,36]. The main reasons for scoring poorly on quality assessment were: a lack of detail regarding how the activity exposures were measured; insufficient information about how the participants were classified into groups exposed to more or less demanding physical activities; insufficient information about selection criteria; and failure to adjust for potential confounders in the analyses. One study reported exposure to LTPA more precisely than was the case for exposure to physicallydemanding occupational activities (not stated how many people actually returned to the occupations post-operatively) and therefore, according to our quality assessment criteria, needed to be scored differently for the purposes of this review [28]: it was graded acceptable quality for LTPA but poor quality for occupation. The quality scoring for the remaining papers were as follows: two were rated as "high quality", six "acceptable", one "poor" and three "very poor".
The number of study participants ranged from 18 [33] to a maximum of 2,016 [37], and the post-operative follow-up from 4.9 [27] to 11 years [33,38]. The average age of patients at the time of surgery was between 55 and 73 years, with primary osteoarthritis (OA) as the main indication (prevalence >60%) for both THA and TKA. Overall, studies recruited more women than men.
Definition of the outcome differed between studies. For some authors, revision included all revision TKA procedures [37,38] recorded in the registries and one of THAs included "a

PLOS ONE
Physically demanding occupational or leisure activities and risk of lower limb arthroplasty revision revision THA performed for any reason" [26]. For others, it was specifically described as a failure of the femoral acetabular component [29]. Five studies only included hip revision procedures for aseptic loosening [27,[30][31][32][33]. There was disparity amongst these studies, however: one focused on aseptic loosening of the femoral component [30] and another on aseptic loosening of either the femoral, acetabular, or both components [32].

Occupation and occupational activities
Findings from studies that examined the risk of arthroplasty revision surgery and occupation or occupational activities are presented in Table 2.
Pre-operative exposure to occupational activities. Three cohort studies assessed preoperative occupational exposures and the risk of revision hip arthroplasty [29][30][31]. The first study, by Maurer et al, rated of moderate quality, [30] categorised male recipients according to the nature of the physical activity performed in their pre-operative job: "no (or little) physical stress" as compared with"physically stressful or agricultural work". Unfortunately, the criteria by which the categories were defined were not stated. The rates of revision surgery were then compared amongst male THA recipients exposed to physical stress/ in farm work, those exposed to no (or little physical stress), and all female THA recipients. The authors reported that, compared with women, men had a 3-fold increased risk of THA revision when exposed to little or no physical stress (RR: 3.15 95%CI 1.70-5.80), and a 5-fold increased risk when exposed to physical stress/agricultural work (RR: 5.24 95%CI 2.80-9.80). The duration of follow-up varied between 5 and 10 years according to the type of stem implant received.
The second study (rated poor quality), by Inoue and colleagues [29] reported a higher risk of hip revision at a mean follow-up of 7.5 years post-THA for those working in agriculture at the time of THA compared with those not working in agriculture. The risk was highest for women working in agriculture compared with women not working in agriculture (RR:3.09, p = 0.04).
In the third study (rated acceptable quality), Flugsrud et al. [31] used occupational exposure collected during a cardiovascular screening assessment, carried out a median of 15 years before THA, and at least 6 years pre-operatively (in 95% of the cases). The mean age at primary THA was 63 years, whereas the mean age at censoring or event (revision) was 68 years. The authors found no association between either intensive, intermediate or moderate physical activity at work and the risk of revision for aseptic loosening of the cup or stem when compared with sedentary work.
A case-control study [28] (rated poor quality) found that, among women, exposure to selfreported "heavy work" before and after arthroplasty was associated with higher rates of THA revision (OR: 1.9, 95%CI 1.2-3.2). In terms of occupation type, they reported that women in health service jobs and those performing domestic work were at higher risk of revision surgery compared with women doing domestic work only (OR: 2.5, 95%CI 1.2-5.1). Other job titles (i.e., women in industry, engineering or construction work) were not found at higher risk.
Cumulatively, three of these studies provide some low-quality evidence that individuals doing physically-demanding work at least at the time of their primary THA (and presumably in many cases also after the surgery) may have a greater risk of subsequent revision. In particular, "heavy" work, agriculture and, in women, health services work, appeared to increase the risk. However, none of these studies provided complete information as to how many THA recipients (male or female) actually returned to their pre-operative occupation after surgery, and whether or not it was at the same or lower intensity compared with pre-operatively. In addition, one acceptable quality study found no association [31].
Post-operative exposure to occupational activities. Only one study clearly measured only post-operative occupational exposures and it was in relation to the risk of revision after primary TKA. Jones et al., in a study rated high quality, investigated the risk of revision TKA in relation to historical occupational activity over an average period of 4 years (SD ± 2) [36]. They found no association between working in occupations with a higher number of metabolic equivalent (MET) hours of physical activity/week and the risk of primary TKA revision.

Leisure-time physical activities (LTPA)
Five studies examined the effect of leisure-time activities on the risk of revision of hip and knee arthroplasty. Table 3 summarises the results for exposure to LTPA and risk of lower limb arthroplasty revision. Pre-operative leisure-time physical activity. Three studies evaluated pre-operative sports or LTPA in relation to risk of revision after hip arthroplasty [28,29,31]. Flugsrud et al. [31] found that men who participated in intermediate/intensive physical activity before THA were at increased risk of cup revision compared with sedentary men (RR: 4.8, 95%CI 1.3-18.2) [31]. In contrast, Inoue et al, rating pre-operative exposure to LTPA as "none" or "some" activity found no association between these levels of recreational activities before THA and risk of subsequent arthroplasty failure (RR:0.89, 95%CI 0.40-1.98) [29]. Unfortunately, neither of these papers provided specific information about the likelihood that THA recipients returned to the same level of physical activity post-operatively, hindering interpretation of these results.
Espehaug et al. [28], rated as acceptable quality, collected data about recreational activities performed before the hip symptoms started and found no association between participation in competitive sports before the primary operation and risk of THA revision (OR: 1.3, 95%CI 0.9-2.1). However, in terms of frequency of recreational activity, men (but not women) doing exercise on a regular basis (weekly) before THA were found to be at increased risk of a THA revision (OR: 2.6, 95%CI 1.4-4.7) compared with those not exercising on a regular basis.
Post-operative exposure to leisure-time physical activity. Espehaug et al found that amongst men and women reporting regular exercise post-THA, there was no associated increased risk of revision post-THA (OR:0.8 95%CI 0.5-1.0) [28]. Dubs et al. [26], in a study rated of poor quality, collected data on sporting activities both pre-and post-THA, but the precise definition of practising sport "regularly" was not stated, nor were the type of questions or scale used to collect the data. They found no significant effect of participation in sport on the risk of THA but did find a strong tendency for the active group to be less likely to need hip revision during the follow-up (14.3% non-active vs 1.6% sports participators).
Only one paper assessed post-operative LTPA in relation to the risk of TKA revision. Jones and colleagues [36] recorded the average number of hours that people engaged in 39 leisure and sport activities post-operatively after TKA. Their results showed no increased risk of TKA revision in participants doing high-intensity leisure activities (OR: 0.96, 95%CI 0.88-1.05).
Taken together, there is no convincing evidence that post-operative LTPA increases the risk of revision after THA or TKA.

Total physical activity
Of the thirteen studies retrieved, eight evaluated the effect of level of total physical activity or a combination of work and leisure activities, on the risk of revision surgery: four after knee arthroplasty and four after hip arthroplasty (Table 4).
Pre-operative total physical activity. Two studies investigated the risk of subsequent revision TKA based upon the total activity exposure reported by participants at the time of their primary surgery. In one study [37], rated of moderate quality, the Lower-Extremity Activity Scale (LEAS) was used to classify participants as physically "active" (LEAS 13 to 18) or "inactive" (LEAS 7 to 12) at the time of their TKA. These investigators found that at 2 years,  Not specified High impact sport vs low impact activities: OR; 3.64 (95% CI, 1.49-8.9) (Continued )   69.5% of the inactive patients and 27.3% of the active patients improved their baseline activity level (p<0.0001). In the crude analyses, aseptic failure rate was 6.3% in the low activity group and 25% in the high-activity group (p = 0.238). At 5 to 10 years' post-operation, the revision rate for all causes (including infection) was different between the active and inactive groups (p = 0.019), whereas revision rate for all non-infective causes was not statistically significantly different between active and inactive groups. In the second study (rated of very poor quality) activity levels were categorised according to the Old-age, Survivors, and Disability Insurance (OASDI) classification, grouping OASDI activity levels 0 to 3 as "sedentary" and 4-7 as "higher activity levels" [35]. The authors reported that participants undergoing TKA revision had a higher activity level at the time of the primary operation than those who did not require revision. Unfortunately, the paper provided no indication as to how active participants were after their primary operation. Post-operative total physical activity. Three studies used the University of California Los Angeles (UCLA) activity scale to capture the level of total physical activity post-THA in relation to risk of revision. The first study, of acceptable quality, [32] showed that, amongst 44 of 433 patients who developed femoral osteolysis, revision for aseptic loosening was more likely with increasing levels of UCLA activity post-operatively measured at 5-or 10-year follow-up. The second study [33], also of acceptable quality, reported that people doing UCLA-rated high impact activities (this includes high-impact sports such as jogging and/or heavy labour [40]) were three times more likely to undergo hip revision compared with those who engaged only in low impact activities (OR:3.64, 95%CI 1.49-8.9) [33]. The third study, with a high methodological quality score, found no association between either the level or frequency of any physical activity post-THA, and the risk of revision [34].
Another study, rated poor quality, [27] classified participants as "active" or "less active", defining them as "active" if they either regularly participated in sports or heavy labour for a period of several years following their total THA. The authors reported that the activity information was obtained from medical records, or by phone and letter contact, and/or patient examination ( Table 4). The authors reported a more than doubling of the risk of revision amongst those who were active when compared with the less active group.
In their study of risk of revision after TKA, Jones et al reported no difference between the level or frequency of historical physical activities (both work and leisure) among people who had undergone TKA revision compared with those who had not, and no association between high levels of historical physical activity and the risk of revision surgery [36]. However, another study rated [38] of moderate quality found that survival rate due to aseptic loosening was better amongst knee arthroplasty recipients with a high level of physical activity (UCLA 6 to 10) compared with those with a low level of physical activity (98.4% (95%CI 97.9-98.9) vs 96.3% (95%CI 95.6-97), p = 0.02). This study included participants followed-up for a minimum of 5 years but also those who underwent a revision procedure within 5 years.
In summary therefore, we found conflicting evidence with respect to total post-operative activity levels and an increased risk of revision after hip and knee arthroplasty.

Discussion
This systematic review examined the evidence about exposure to high-intensity or physicallydemanding activities either at work or in leisure-time and the risk of hip or knee revision surgery. From 11,307 studies identified as of interest, 13 fulfilled our inclusion/exclusion criteria. Amongst five studies exploring the role of occupation (or occupational activities) after hip arthroplasty, two reported a positive association with pre-operative farming [29,30]; one reported an increased risk with heavy physical work (pre and post-THA) [28], and one no effect [31]. The only study of occupational activities after TKA found no association [36]. For revision THA with sports and LTPA participation, 4 studies were inconsistent: two found increased risk [28,31], (only amongst men) [28]; one found no effect [29]; and one (poor-quality) study found reduced risk [26]. Three studies evaluated THA revision and total activities (work and leisure) using the same measurement tool (UCLA) but were also conflicting: one suggested an increased risk with increasing activity [32]; one suggested an increased risk with high-impact sport [33]; and the best quality study found no effect for either level or intensity of activities [34]. Another (weak) study measured total activities with a different tool and reported a doubling of risk of revision THA [27]. For LTPA after TKA, one study found no association [36], another found better implant survival with more physical activity [38], one found that total physical activity at the time of TKA increased risk of revision for all causes, but not after exclusion of those performed for infectious causes [37] and another (poor quality) study reported that LTPA increased the risk of revision [35]. Taken together, we found a heterogeneous literature unsuitable for pooling for quantitative synthesis. The evidence is unconvincing for an increased risk of revision after hip or knee arthroplasty associated with LTPA, and although there is some evidence for increased risk of revision THA with physicallydemanding work, more research is required using standardised methodology. In particular, more studies are needed after TKA.
We experienced methodological challenges in assessing the evidence. Firstly, to address our research question, the exposure to physical activity should ideally be measured both before and after lower limb arthroplasty, since accounting only for pre-operative work or leisure physical activity may lead to misclassification of the post-operative exposure. People who were very active pre-operatively may not necessarily be able to achieve the same level of activity post-operatively and vice versa. Certainly, pooled data from 4 studies which examined engagement with sport amongst THA patients indicated that, overall, 18% of people did not resume such activities post-operatively [41]. Additionally, three reviews found a reduction in the intensity or impact of sports participation among patients post-operatively [41][42][43]. Generally, most people working pre-operatively return to work after arthroplasty [41], but they may move to a different, occupation [44,45], involving less-physically demanding activities. In order to address our research question more effectively, researchers need to more clearly collect actual exposure data using reliable methods. Secondly, the definition of revision arthroplasty, and the indication for carrying out revision, varied between the studies. In the majority, the main indication for revision was aseptic loosening, but a few studies used a broader definition [26,28,34]. Ollivier et al, for example, defined implant failure as "hip revision in the presence of radiographic signs of aseptic loosening" [33]. Thirdly, investigators in these studies used a wide variety of methods and measurement tools to collect information about exposure to work and leisure activities, which precluded comparison of results between studies, not least because each instrument (often non-standardised) referred to a different recall period of activity. Those studies which attempted to measure occupational exposures used job title or subjective assessments such as "heavy work". Neither of these types of methods has good reliability or validity for the assessment of true occupational exposure [46] and more high-quality data collection in this area is desperately needed. Equally, participation in LTPA can vary markedly, even when individuals ostensibly report the same sporting activity e.g., tennis or running/jogging. Future studies need to include more detailed measures which either better identify specific loading of the joints in question or at least more accurately quantify the intensity and duration of the exposures over time. Use of the UCLA activity score might have facilitated comparison of the results from three of the retrieved studies but, as already observed, researchers reported their results differently. Arguably an "overall" activity level is less helpful for advising patients compared to a separate assessment of work and LTPA.
Unfortunately, there are no clinical or consensus guidelines about the resumption of postoperative occupational activities (likely because of the lack of evidence). A recent qualitative study found that surgeons tend to assume that most arthroplasty recipients have retired and only a small minority are employed who wish or need to RTW post-operatively [47]. However, they acknowledged that they are likely to see an increasing number of patients who expect to return to work post-operatively and they agreed that they currently provide limited occupational advice to patients, which was largely based upon whether the individual undertook deskbased work as compared with any other type of work [47]. In some cases, they suggested that they might advise patients with manual jobs to consider changing their occupation, particularly if specific activities were involved e.g., kneeling. It is widely acknowledged that work is important to health and financial stability [48]. Many governments have made legislative changes to encourage people to work to older ages so that in the UK, for example, people will only be entitled to claim their state pension at 67 years of age or above rising to 68 for those born after April 1978. Therefore, working post-arthroplasty is set to become a more common phenomenon and the current review reveals the size of the evidence gap and the growing need for carefullydesigned research that accurately measures post-operative occupational activities and the risk of revision in order to enable surgeons to give constructive advice to future patients.
Interpretation of the findings of this review must consider some limitations. We limited our search to include only those studies published following a peer-reviewed process, choosing to exclude articles published in the grey literature. Whilst this may increase the risk that our findings are affected by publication bias, the likelihood of this is somewhat reduced in that relatively few of the included papers investigated the role of occupational and/or leisure-time activities as their primary factors of interest. Indeed, if anything, leisure-time activities and sports participation were more often included in the title of papers and our findings show that, despite this, we could not find convincing evidence of their association with the risk of revision surgery. The authors acknowledge that omission of the grey literature here may have limited the comprehensiveness of our review. Additionally, the search was limited to publications in English or Spanish and therefore may have missed studies published in other languages, although key papers are more likely to be published in English. Unfortunately, we were only able to perform a narrative synthesis of the evidence rather than a quantitative analysis for a range of reasons including: the heterogeneity of the time frame of measurement of occupational/physical activities (pre-operative, perioperative and post-operative) the wide variation in the methods of assessment of these activities; the small number of studies that addressed leisure-time and occupational activities separately; and the variability of the duration of postoperative follow-up (ranged from a minimum of 4.9 years to a maximum of 11 years). Furthermore, unfortunately, revision was only a secondary outcome in three of the included studies [30,32,37]. As the risk of revision has declined with improved materials and surgical techniques, so statistical power to detect risk is diminished unless large-scale studies are carried out, with a very long duration of follow-up. It is for this reason that arthroplasty registers have been set up [49] and these could provide an ideal framework for investigating the current research questions. Despite these limitations, the current review is, to the best of our knowledge, the first to examine the effect of occupation and leisure activities on the risk of lower limb arthroplasty revision.

Conclusion
In summary, the findings from this review highlighted the paucity of relevant studies on this research question, especially for revision surgery after TKA. Many studies only assessed relevant exposure pre-operatively, which is likely to be of limited relevance to post-operative activities. Based on the limited evidence identified, occupation and leisure-time physical activity do not convincingly increase the risk of revision after hip or knee arthroplasty. Given the lack of evidence and the inconsistencies found, more research is needed to assess the risk of mechanically loading the replaced hip or knee following joint arthroplasty, and, in particular, to investigate the impact of return to physically-demanding occupational activities, given that increasing numbers of people will want and need to return to work post-arthroplasty.
Supporting information S1 File. MeSH terms and keywords used in the search. (DOCX) S1